Coupling AFM,DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study

Polymeric film-forming systems have emerged as an esthetically acceptable option for targeted, less frequent and controlled dermal drug delivery. However, their dynamic nature (rapid evaporation of solvents leading to the formation of thin films) presents a true characterization challenge. In this study, we tested a tiered characterization approach, leading to more efficient definition of the quality target product profiles of film-forming systems. After assessing a number of physico-chemico-mechanical properties, thermal, spectroscopic and microscopic techniques were introduced. Final confirmation of betamethasone dipropionate-loaded FFS biopharmaceutical properties was sought via an in vitro skin permeation study. A number of applied characterization methods showed complementarity. The sample based on a combination of hydrophobic Eudragit^® RS PO and hydroxypropyl cellulose showed higher viscosity (47.17 ± 3.06 mPa·s) and film thickness, resulting in sustained skin permeation (permeation rate of 0.348 ± 0.157 ng/cm² h), and even the pH of the sample with Eudragit^® NE 30D, along with higher surface roughness and thermal analysis, implied its immediate delivery through the epidermal membrane. Therefore, this study revealed the utility of several methods able to refine the number of needed tests within the final product profile.     

The Role of Heparan Sulfate in CCL26-Induced Eosinophil Chemotaxis

Proinflammatory chemokine ligand 26 (CCL26, eotaxin-3) mediates transendothelial cell migration of eosinophils by binding and activating the G-protein-coupled (GPC) chemokine receptor 3 on the surface of eosinophilic cells. Here we have investigated the role of glycosaminoglycans (GAGs) as potential co-receptors in the process of CCL26-induced eosinophil chemotaxis. For this purpose, we have first identified the GAG-binding site of CCL26 by a site-directed mutagenesis approach in the form of an alanine screening. A panel of GAG-binding-deficient mutants has been designed, generated, and analyzed with respect to their binding affinities to heparan sulphate (HS) by isothermal fluorescence titration studies. This showed that basic amino acids in the α-helical part of CCL26 are strongly involved in GAG-binding. In chemotaxis experiments, we found that decreased GAG-binding affinity correlated with decreased chemotactic activity, which indicates an involvement of GAGs in eosinophil migration. This was further proven by the negative impact of heparinase III treatment and, independently, by the incubation of eosinophils with an anti heparan sulfate antibody. We finally investigated eosinophils’ proteoglycan (PG) expression patterns by real-time PCR, which revealed the highest expression level for serglycin. Including an anti-serglycin antibody in CCL26-induced eosinophil migration experiments reduced the chemotaxis of these immune cells, thereby proving the dependence of eosinophil mobilization on the proteoglycan serglycin.     

Structural Analysis of Mitochondrial Dynamics—From Cardiomyocytes to Osteoblasts: A Critical Review

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.     

Cocaprins, β-Trefoil Fold Inhibitors of Cysteine and Aspartic Proteases from Coprinopsis cinerea

We introduce a new family of fungal protease inhibitors with β-trefoil fold from the mushroom Coprinopsis cinerea, named cocaprins, which inhibit both cysteine and aspartic proteases. Two cocaprin-encoding genes are differentially expressed in fungal tissues. One is highly transcribed in vegetative mycelium and the other in the stipes of mature fruiting bodies. Cocaprins are small proteins (15 kDa) with acidic isoelectric points that form dimers. The three-dimensional structure of cocaprin 1 showed similarity to fungal β-trefoil lectins. Cocaprins inhibit plant C1 family cysteine proteases with K_i in the micromolar range, but do not inhibit the C13 family protease legumain, which distinguishes them from mycocypins. Cocaprins also inhibit the aspartic protease pepsin with K_i in the low micromolar range. Mutagenesis revealed that the β2-β3 loop is involved in the inhibition of cysteine proteases and that the inhibitory reactive sites for aspartic and cysteine proteases are located at different positions on the protein. Their biological function is thought to be the regulation of endogenous proteolytic activities or in defense against fungal antagonists. Cocaprins are the first characterized aspartic protease inhibitors with β-trefoil fold from fungi, and demonstrate the incredible plasticity of loop functionalization in fungal proteins with β-trefoil fold.     

Complex‐Shaped Cellulose Composites Made by Wet Densification of 3D Printed Scaffolds

Cellulose is an attractive material resource for the fabrication of sustainable functional products, but its processing into structures with complex architecture and high cellulose content remains challenging. Such limitation has prevented cellulose‐based synthetic materials from reaching the level of structural control and mechanical properties observed in their biological counterparts, such as wood and plant tissues. To address this issue, a simple approach is reported to manufacture complex‐shaped cellulose‐based composites, in which the shaping capabilities of 3D printing technologies are combined with a wet densification process that increases the concentration of cellulose in the final printed material. Densification is achieved by exchanging the liquid of the wet printed material with a poor solvent mixture that induces attractive interactions between cellulose particles. The effect of the solvent mixture on the final cellulose concentration is rationalized using solubility parameters that quantify the attractive interparticle interactions. Using X‐ray diffraction analysis and mechanical tests, 3D printed composites obtained through this process are shown to exhibit highly aligned microstructures and mechanical properties significantly higher than those obtained by earlier additively manufactured cellulose‐based materials. These features enable the fabrication of cellulose‐rich synthetic structures that more closely resemble the exquisite designs found in biological materials grown by plants in nature.     

Synchrophasor communication

Synchronized phasor measurements provide the basis for fine-grained wide area power quality monitoring in electric grids. Time-synchronized phasor measurement units (PMUs) are deployed at different locations in the grid and report 10–60 measurements/second to energy management systems or other applications. For control applications it is crucial to receive measurement data as soon as possible after a state change in order to trigger corrective actions in time to prevent incidents in the grid. In this paper we analyze characteristics of synchrophasor M2M communication for different network technologies, including VDSL, HSPA and LTE networks. We briefly review synchrophasor communication approaches and real-time demands. We then emulate PMU traffic and perform measurements on different networks. We show how the underlying technology influences one-way delay patterns for synchrophasor communication, which has direct implication on the achievable real-time properties.     

Lithium Tin Sulfide—a High‐Refractive‐Index 2D Material for Humidity‐Responsive Photonic Crystals

Extending the portfolio of novel stimuli‐responsive, high‐refractive‐index (RI) materials besides titania is key to improve the optical quality and sensing performance of existing photonic devices. Herein, lithium tin sulfide (LTS) nanosheets are introduced as a novel solution processable ultrahigh RI material (n = 2.50), which can be casted into homogeneous thin films using wet‐chemical deposition methods. Owing to its 2D morphology, thin films of LTS nanosheets are able to swell in response to changes of relative humidity. Integration of LTS nanosheets into Bragg stacks (BSs) based on TiO₂, SiO₂, nanoparticles or H₃Sb₃P₂O₁₄ nanosheets affords multilayer systems with high optical quality at an extremely low device thickness of below 1 µm. Owing to the ultrahigh RI of LTS nanosheets and the high transparency of the thin films, BSs based on porous titania as the low‐RI material are realized for the first time, showing potential application in light‐managing devices. Moreover, the highest RI contrast ever realized in BSs based on SiO₂ and LTS nanosheets is reported. Finally, exceptional swelling capability of an all‐nanosheet BS based on LTS and H₃Sb₃P₂O₁₄ nanosheets is demonstrated, which bodes well for a new generation of humidity sensors with extremely high sensitivity.